Evaluation of MCAO stroke models in normotensive rats: standardized neocortical infarction by the 3VO technique

The temporary three-vessel occlusion (3VO) technique with a surgical approach for middle cerebral artery (MCA) produces consistent cerebral infarction in the neocortex in normotensive rats. The intraluminal thread-occlusion technique with an endovascular approach targeting the MCA occlusion (MCAO) is more widely used since it does not require complicated intracranial procedures. The aim of this study was to review the methods/models for MCAO stroke in normotensive rats and to evaluate a 3VO stroke model that provides consistent degrees and variance of cortical stroke injury for additional discussion. First, we analyzed a model with modified temporary 3VO technique requiring less complicated procedures than the temporary 3VO model, i.e., temporary occlusion of the bilateral common carotid arteries (CCAs) superimposed on a permanent occlusion of the MCA, in Sprague-Dawley rats or C57BL/6J mice. In the microvascular tissue (cerebral) perfusion study, significant reductions in regional cerebral perfusion during the 3VO accompanied a rapid return to baseline after release of the CCAs, showing that the technique induces temporary focal ischemia. The average sizes and variances of the neocortical infarction in this model, together with those in the other normotensive rat models caused by the 3VO technique in the literature, indicated a standard size and variance of infarcted lesion in the control groups relative to the specific ischemic period. However, stroke injuries in the neocortex induced by the thread occlusion technique showed greater variability with less consistent lesion sizes. Inclusion/exclusion criteria to avoid inappropriate cases with too mild (no/faint infarction) or too great (huge/fatal infarction) severity in the ischemic injury may differ between laboratories in the thread occlusion model.